What are blood clots?

What are blood clots? Dr Matthew Fay GP Principal The Willows Medical Practice- Queensbury GPwSI and Co-Founder Westcliffe Cardiology Service GP Partner Westcliffe Medical Group Created 5/31/18 Dr. Matthew Fay: Affinity Care

What is a blood clot? Is a vital part of our system that keeps the blood in the pipes

What is a Thrombus? Solid mass of blood constituents Formed within the vascular system In life

Thrombus is different to Clot! Clotting means coagulation which can occur within or outside the vascular system in life or post mortem.

Why does Thrombus occur? Abnormalities of the vessel wall atheroma direct injury inflammation

Why does Thrombus occur? Abnormalities of blood flow stagnation turbulence Abnormalities of blood components smokers post-partum post-op

Lets form a Thrombus What do we need Blood Stimulation

Lets form a Thrombus What do we need Blood Stimulation Vessel wall damage Vasoconstriction Stagnation of the blood

Lets form a Thrombus What do we need Blood Stimulation Vessel wall damage Vasoconstriction Stagnation of the blood Exposure of the collagen and/or fibrin

Platelet activation Lets form a Thrombus

Lets form a Thrombus Platelet activation Derived from megakaryocytes in bone marrow No nucleus Contain Alpha granules (adhesion substances) Dense granules (aggregation substances)

Lets form a Thrombus On contact with fibrin or collagen platelets release granules which promote aggregation of adjacent platelets to form a mass which covers, for example, an endothelial defect. Contact with Fibrin or Collagen Release Granules Aggregate to form a mass E.g. Covering Endothelial Defect

Lets form a Thrombus Platelet aggregation in this way is a normal phenomenon, and occurs continuously in the body to repair minor endothelial injury. Contact with Fibrin or Collagen Release Granules Aggregate to form a mass E.g. Covering Endothelial Defect

Not the whole story! Lets form a Thrombus

Lets form a Thrombus Stimulation Vessel wall damage Vasoconstriction Stagnation of the blood Exposure of the collagen and/or fibrin

Lets form a Thrombus What happens next (simplified)

Lets form a Thrombus Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Thrombinase Fibrinogen (soluble) Factor Va Thrombin Fibrin (insoluble)

Lets form a Thrombus Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Thrombinase Fibrinogen (soluble) Factor Va Thrombin Fibrin (insoluble)

Lets form a Thrombus 1 ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin Tight regulation therefore required Balance of procoagulant and anticoagulant forces

Lets form a Thrombus-Regulation Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Thrombinase Fibrinogen (soluble) Factor Va Thrombin Fibrin (insoluble)

Lets form a Thrombus-Regulation Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Thrombinase Fibrinogen (soluble) Factor Va Thrombin Protein C Activation Fibrin (insoluble)

Lets form a Thrombus-Regulation Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Thrombinase Fibrinogen (soluble) Factor Va Thrombin Protein C Activation Fibrin (insoluble) Protein S

Lets form a Thrombus-Regulation Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Protein C Activation Fibrin (insoluble) Plasmin Protein S

VENOUS THROMBOSIS: AETIOLOGY Causes of venous thrombosis can be considered under Virchow s triad. The most important site of venous thrombosis is in the deep veins of the leg. DAMAGED VALVE ENDOTHELIUM WALL SLOW IMMOBILITY FLOW BLOOD CONSTITUENTS FIBRINOGEN e.g. POST OP

VENOUS THROMBOSIS: AETIOLOGY Causes of venous thrombosis can be considered under Virchow s triad. After operations, injury or severe illness of many kinds fibrinogen and other coagulation factors in the blood are increased due to increased hepatic synthesis. This leads to an increased risk of deep vein thombosis. SLOW IMMOBILITY DAMAGED VALVE ENDOTHELIUM FLOW WALL BLOOD CONSTITUENTS FIBRINOGEN e.g. POST OP

VENOUS THROMBOSIS: AETIOLOGY Causes of venous thrombosis can be considered under Virchow s triad. DAMAGED VALVE ENDOTHELIUM Slow blood flow promoted by immobility due to chronic illness, or bed rest post-operatively can promote venous thrombosis. SLOW IMMOBILITY FLOW WALL BLOOD CONSTITUENTS FIBRINOGEN e.g. POST OP

VENOUS THROMBOSIS: AETIOLOGY PREDISPOSING FACTORS FOR DEEP VENOUS THROMBOSIS Immobility, bed rest Post op coagulability changes Pregnancy OC pill Severe burns and trauma Cardiac failure Disseminated malignancy Economy class syndrome SLOW IMMOBILITY DAMAGED VALVE ENDOTHELIUM FLOW WALL BLOOD CONSTITUENTS FIBRINOGEN e.g. POST OP

Lets form a Thrombus? Thrombi can occlude a vessel which may result in necrosis of the part served (infarction). Occlusive Infarction Mural thrombus can release fragments (emboli) which can travel in the bloodstream to block distal vessels. Mural Embolism Thrombus on heart valves due to infection can also embolise. Vegetation 30 Embolism

OUTCOMES OF THROMBOSIS 1 THROMBOLYSIS Thrombosis can be cleared by the fibrinolytic system. Plasminogen activator released from endothelial cells converts plasminogen to plasmin which dissolves fibrin. Lysis Recanalisation Fibrosis Embolism 31

OUTCOMES OF THROMBOSIS 2 RECANALISATION Thrombosis can undergo recanalisation. Endothelial cells grow out from the vessel wall and create new channels through the thrombus: Lysis Recanalisation Fibrosis Embolism 32

EMBOLISM OUTCOMES OF THROMBOSIS 3 Lysis Fibrosis Thrombosis can throw off emboli which can occlude distal vessels Recanalisation Embolism 33

OUTCOMES OF THROMBOSIS 4 FIBROSIS: ORGANISATION Thrombosis can simply be organised i.e undergo fibrous tissue replacement Lysis Fibrosis Recanalisation Embolism 34

Propagation progressive spread of thrombosis distally in arteries proximally in veins OUTCOMES OF THROMBOSIS 5 35

Lets form a Thrombus-Malfunctions Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Protein C Activation Fibrin (insoluble) Plasmin Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Protein C Activation Fibrin (insoluble) Plasmin Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Aspirin Factor Xa Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Protein C Activation Fibrin (insoluble) Plasmin Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Heparins Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Heparins Fibrin (insoluble) Plasmin Protein C Activation Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Warfarin Factor IX Warfarin Factor VIII Warfarin Platelets Factor Xa Prothrombin Fibrinolysis Factor Va Thrombinase Thrombin Warfarin Fibrinogen (soluble) Plasminogen Protein C Activation Warfarin Fibrin (insoluble) Plasmin Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Dabigatran Fibrin (insoluble) Plasmin Protein C Activation Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Xabans Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Protein C Activation Fibrin (insoluble) Plasmin Protein S

Lets NOT form a Thrombus-Treatment Collagen /fibrin exposed Factor VII Factor IX Factor VIII Platelets Factor Xa Prothrombin Fibrinolysis Thrombinase Fibrinogen (soluble) Plasminogen Factor Va Thrombin Protein C Activation Protein S Fibrin (insoluble) Thrombolysis Plasmin

What is a blood clot-summary Is a vital part of our system that keeps the blood in the pipes Collagen /fibrin exposed Factor VII Lets form a Thrombus-Regulation Protein C Activation Protein S Factor IX Factor Xa Factor Va Factor VIII Collagen VENOUS THROMBOSIS: AETIOLOGY Causes of venous thrombosis Factor VII can /fibrin be considered exposedunder Virchow s triad. Prothrombin The most important site of venous thrombosis Thrombinase is in the deep veins of the leg. Lets NOT form a Thrombus-Treatment Warfarin Thrombin Protein C Activation Warfarin Factor IX Warfarin Factor Xa Fibrinogen (soluble) Fibrin Factor Va (insoluble) Factor VIII Warfarin SLOW IMMOBILITY DAMAGED VALVE ENDOTHELIUM Fibrinolysis Plasminogen FLOW Plasmin WALL Thrombinase BLOOD CONSTITUENTS Prothrombin Thrombin Warfarin FIBRINOGEN e.g. POST OP Dabigatran Fibrinogen (soluble) Fibrin (insoluble) Fibrinolysis Plasminogen Plasmin Protein S

The important thing is not to stop questioning. Curiosity has its own reason for existing Albert Einstein Thank you for your attention Questions? matthew.fay@bradford.nhs.uk